HODGKIN’s LYMPHOMA

Question 1

INTRODUCTION

Answer 1

The hematopoeitic system is traditionally divided into:
the myeloid tissue, which include the bone marrow and the cells derived from it: red cells, platelets, granulocytes, monocytes; and
The lymphoid tissue, consisting of the thymus, lymph nodes, and spleen.

—The thymus gland is a pink, lobulated lymphoid organ, located in the thoracic cavity and neck of children and adolescents. Involved in development of immune system

Question 2

DISORDERS OF THE THYMUS GLAND

Answer 2

Disorders of Thymus gland includes

-Developmental disorders(Thymic hypoplasia or Aplasia and Thymic cysts)
-Thymic hyperplasia
-Thymoma

DEVELOPMENTAL DISORDERS
+Thymic hypoplasia or aplasia: variable defects involving the heart and great vessels: these changes occur in DiGeorge syndrome.
+Thymic cysts: The are uncommon lesions lined by stratified or columnar epithelium; they are mostly developmental in origin. They occassionally herald an adjacent thymic neoplasm, especially lymphoma or thymoma.

THYMIC HYPERPLASIA
Thymic hyperplasia refers to the appearance of reactive B-cell lymphoid follicles within the thymus.
It is seen in chronic inflammatory and immunologic states, particularly myasthenia gravis (65% to 75% of cases).

THYMOMAS
Thymomas are neoplasm derived from thymic epithelial cells. These may be:
1.Cytologically benign and noninvasive
2. Cytologically benign but invasive and metastatic
3. Cytologically malignant (thymic carcinoma)

GROSS;
Lobulated, firm, gray white masses, they exhibit focal cystic necrosis and calcification
Most are encapsulated

MICROSCOPIC
NON INVASIVE; composed of medullary or cortical epithelial cells often with a sparse THYMOCYTE infiltrate
INVASIVE; more commonly exhibit cortical type epithelial cells and more numerous THYMOCYTE infiltration

Thymic carcinoma:
Represents 5% of thymomas
They are fleshy, invasive masses that are commonly squamous cell carcinomas
The second most common variant is lymphoepthelioma-like carcinoma, microscopically resembling nasopharyngeal carcinoma, and in 50% of cases containing monoclonal EBV genome.

CLINICALFEATURES AND TREATMENT

Question 3

THE SPLEEN

Answer 3

—The spleen is the largest organ of the lymphatic system

Its four main functions that impact disease state include:
-Phagocytosis of blood cells and particulate matter
-Antibody production
-Hematopoiesis
-Sequestration of formed blood elements.

The main pathology involving the spleen include:
1.Splenomegaly
2.Nonspecific Acute Splenitis (with any bloodborne infection)
3.Congestive Splenomegaly (RHF, cirrhosis, extrahepatic portal vein obstruction –thrombosis, pylephlebitis).
4.Splenic Infarcts(embolic infarct in endocarditis & severe atherosclerosis; splenomegaly compromises intrasplenic blood flow).
5.Neoplasms(myeloid & lymphoid tumours; benign: fibromas, osteomas, chondromas, lymphangioma, hemangoima).
6.Congenital Anomalies(hypoplasia, accessory spleen or in situs inversus).
7.Rupture (following blunt force injury)

DISORDERS ASSOCIATED WITH SPLENOMEGALY
—Infections
Malaria
Leishmaniasis
Schistosomiasis
Trypanosomiasis
Syphilis
Typhoid
TB
— Congestive states
Liver cirrhosis
Cardiac failure
Splenic vein thrombosis
—Lymphohematogenous disirders
Hodgkin lymphoma
Non hodgkin lymphoma
Multiple myeloma
— Immunologic inflammatory conditions
Rheumatoid arthritis
SLE

Amyloidosis

Question 4

LYMPH NODES

Answer 4

The lymph nodes are kidney shaped structures (0.1cm to 2.5cm long) that act to filter foreign particles from the blood.
They play an important role in the immune response to infection
There are about 400 to 450 different lymph nodes in the body; majority are located within the abdomen.

Some of lymph nodes pathology include: (EPIIVNN)
1-Ectopic tissue/inclusions (e.g., epithelial inclusions,mesothelial, mullerian, salivary gland, smooth muscle, etc.)
2-Pigment/foreign material (eg., anthracosis, iron, lipofusion, melanosi, etc)
3-infectious/parasitic disorders(eg.,HIV, EBV, TB, Leprosy,etc)
4-Inflammatory/reactive disorders (acute and chronic nonspecific lymphadenitis)
5-Vascular lesions (eg., angiomyoliopma, lymphangioma, etc)
6-Non-specific findings.(reactive lymphadenopathy, lymphohistiocytosis, inflammatory pseudotumor, etc)
7-Neoplasms (lymphoma, amyloid, histiocytic sarcoma, plasmacytoma, CML, leiomyoma, etc).

LYMPHADENOPATHY/LYMPHADENITIS
A. ACUTE NONSPECIFIC LYMPHADENITIS:
-Tender enlargement of lymph nodes
-Focal involvement is seen with bacterial lymphadenitis.
Histology: may see neutrophils within the lymph node
Generalized involvement of lymph nodes is seen with viral infections ( one sees reactive T-cell immunoblasts in lymph nodes and peripheral blood.

B. CHRONIC NONSPECIFIC LYMPHADENITIS:
-Nontender enlargement of lymph nodes
-Follicular hyperplasia involves B-lymphocyte and may be seen with rheumatoid arthritis, toxoplasmosis, and early HIV infections.
-Paracortical hyperplasia involves T cells and may be seen with viruses, drugs (Dilantin), and sytemic lupus erythematosus (SLE).
-Sinus histiocytosis involves macrophages and, in most cases, is nonspecific. An example is lymph nodes draining cancers.

Question 5

LYMPHOID NEOPLASMS

Answer 5

Leukemias are neoplasms with widespread involvement of bone marrow and often (but not always) the peripheral blood.
Lymphomas are proliferations that arise as discrete tissue masses (e.g, within lymph nodes, spleen, or extranodal tissues).
*Distinction btw leukemias and lymphoma is blurry.

ACUTE LEUKEMIAS:
Peripheral blood has decreased mature forms and increased immature forms called blasts, which have immature chromatin with nucleoli.
Bone marrow has increased immature cells (blasts); the diagnostic criteria is >30% blasts in the bone marrow.
Acute symptoms are secondary to marrow failure, which can produce decreased RBCs (causing anemia and fatigue), decreased WBCs (permitting infections and fever), and decreased platelets (inducing bleeding)

There are two broad categories of lymphomas viz:
1. Hodgkin lymphoma (HL)
2. Non-Hodgkin lymphoma (NHL)

WHO CLASSIFICATION OF LYMPHOID NEOPLASMS
WHO classification scheme sorts the various lymphoid neoplasms into five broad categories,
REAL classification – 1 to 4 above as NHL.

1. Precursor B(pre-B)- cell neoplasms (immmature B cells)
2. Peripheral B-cell neoplasms (mature B cells)
3. Precursor T (pre-T)-cell neoplasms (immature T cells)
4. Peripheral T-cell and NK-cell neoplasms(mature T cells and NK cells)
5. Hodgkin lymphoma(HL): neoplasms of Reed-Sternbeg (RS) cells.

Question 6

HODGKIN LYMPHOMA

Answer 6

DIFFERENCE BETWEEN HODKIN AND NON HODGKIN LYMPHOMA
-Clinically, HD may present similar to infection (with fever).
-Spread is contiguous to adjacent node groups (unlike NHL).
-Classification is based on inflammatory response and not malignant cell.
-No leukemic state
-Extranodal spread is uncommon

AETIOLOGY
The causes of HL are not known, risk factors include:
1.Familial: siblings of an affected individual have a 3- to 7-fold increased risk of developing HL; the risk is higher in monozygotic twins
2.EBV infection more often in immunocompromised with 5- to 10-fold fold increase in HL incidence, usually aggressive of mixed cellularity or lymphocyte depleted.
3.Agent orange, a carcinogenic exotoxin herbicide and defoliant used by the USA during his war of aggression with Vietnam

NOTE;

The malignant cell is the Reed-Sternberg (RS) cell:
- “Owl-eye” appearance: symmetric (mirror image) bilobed nucleus with prominent central nucleoli surrounded by clear space.
-RS cells are positive for CD15 (Leu M1) and CD30 (Ki-1).
-Except for lymphocytic predominant HD (non-classical HL) in which malignant cells stain for B-cell markers, and have negative CD15 and CD30 expression.

CLASSIFICATION
NON CLASSICAL HL:
1-Nodular lymphocyte predominant type: has L-H cells (popcorn cells) and are negative for CD15 & CD30.

CLASSICAL HL:
1-Mixed cellularity: has eosinophils and plasma cells (increased number of eosinophils is related to IL-5 secretion).
2-Lymphocyte depleted: has few lymphocytes, and there are many RS cells.
3-Lymphocyte rich: rare, assoc. with EBV (40%).
4- Nodular sclerosis (NS): the most common in females, lymph nodes have broad collagen bands. RS variant: lacunar cells.

Question 7

HODGKIN DISEASE: CLINICAL CHARACTERISTICS

Answer 7

1. Bimodal age group distribution (late 20s & >50)
2. Usually patients present with painless enlargement of lymph nodes.
3. B-cell symptoms: fever (that comes and goes = Pel-Ebstein fever), weight loss and night sweats.
4. Bad prognosis is directly proportional to the number of RS cells present and inversely proportional to the number of lymphocytes.
5. Survivors of chemotherapy and radiotherapy have increased risk of non-Hodgkin lymphoma or acute leukemia.